The general objective is to characterize by pharmacological and biochemical methods the adrenergic receptors in selected sympathetically innervated tissues in order to improve our understanding of factors at the receptor level which regulate the responses of these tissues to various adrenergic drugs and to sympathetic nerve stimulation. Experiments will be carried out (1) to ascertain whether the simultaneous occurrence of more than one type of adrenergic beta-receptor in a single cell type is a common phenomenon; (2) to elucidate the factors which control the variable ratio of beta 1- to beta-type receptors in tracheal smooth muscle cells (3) to reexamine whether postjunctional adrenergic alpha-receptors in different sympathetic effectors in the same species are all of a single type; (4) to investigate whether prejunctional alpha-receptors on adrenergic nerve terminals can be differentiated pharmacologically from postjunctional alpha-receptors. Characterization of receptors responsible for mediating a specific response in a given isolated tissue will be carried out by determining with appropriate pharmacological procedures absolute or relative affinities and efficacies of selected agonists, and affinities of selected competitive antagonists. Situations where more than one type of beta-receptor occur in a single cell type will be analyzed by appropriate testing both with competitive antagonists "selective" for either the beta 1- or beta 2-type and with agonists also "selective" for one or the other type. In addition, we shall apply radioactive ligand-binding techniques for quantification of one or more types of beta-receptors (or alpha-receptors) in selected tissues. In addition to adrenergic receptors, some other kinds of receptors whose activation influences peripheral adrenergic mechanisms will be studied. In particular, we will continue investigating muscarinic cholinergic receptors on which acetylcholine acts to produce relaxation of blood vessels.